Tumor-Infiltrating Basophils Are Associated With Improved Prognosis in Colorectal Cancer

Purpose Basophils are rare granulocytic cells known for their role in allergic reactions, but they may also be involved in other diseases such as cancer. However, the role of tumor-infiltrating basophils in colorectal cancer (CRC) remains unexplored. Here, we aimed to clarify the significance of basophils in CRC by analyzing tumor tissue from two CRC cohorts (N=1,830) and blood samples from 730 patients. Materials and Methods Tumor-infiltrating basophils were identified and quantified using double immunohistochemistry (proMBP1 for basophils, cytokeratin for tumor cells) combined with digital image analysis, and blood basophil counts were measured. The associations between basophils (in tumor tissue and blood) and clinicopathological features, prognosis, immune cell profiles, and systemic inflammation markers were examined. Results Higher densities of tumor-infiltrating basophils showed an inverse association with cancer-specific mortality, with stronger evidence in Cohort 2 than in Cohort 1. After adjusting for key prognostic factors (including disease stage and mismatch repair status), the HR for cancer-specific mortality comparing high vs. low basophil density was 0.67 (95%CI 0.43-1.03, p Trend =0.051) in Cohort 1 (N=749), and 0.54 (95%CI 0.40-0.74, p Trend <0.001) in Cohort 2 (N=1,039). Higher basophil densities were also associated with lower disease stage and less frequent lymphovascular invasion but not with mismatch repair deficiency. Blood basophil count correlated with tumor-infiltrating basophil density (r=0.113, p=0.003) but was not associated with prognosis. Conclusion Tumor-infiltrating basophils seem to be associated with favorable clinicopathological features and potentially improved CRC outcomes, suggesting that basophils may contribute to the tumor microenvironment.